The goal of this research program is to understand wound healing and its failure. In preliminary experiments, we analyzed wound fluid from burn wounds, chronic skin ulcers, and mastectomy wounds. The results showed that wound fluid can be used as a non-invasive method to learn about wound repair. During the next four years, we will build on the preliminary studies to answer important questions about the proteinases, adhesion proteins, and growth factors found in would fluid and their biological functions. Specific aims of the project are as follows: to learn if elastase is responsible for degradation of fibronectin in burn wound fluid and chronic ulcer fluid and if there is a defect in the proteinase inhibitor system; to learn if fibronectin fragments in wound fluid stimulate proteinase secretion or have endogenous proteinase activity; to learn if "activated" metalloproteinases in chronic ulcer and burn wound fluid are biologically active; to learn if treatment of mastectomy fluid with "inflammatory" enzymes results in metalloproteinase activation and fibronectin degradation similar to that seen in chronic wound fluid or burn wound fluid; to identify the burn wound fluid growth factor and other factors that modify keratinocyte migration or fibroblast contraction; and to further correlate the relationship between wound fluid composition and clinical healing.